The use of Bayesian latent class cluster models to classify patterns of cognitive performance in healthy ageing

The main focus of this study is to illustrate the applicability of latent class analysis in the assessment of cognitive performance profiles during ageing. Principal component analysis (PCA) was used to detect main cognitive dimensions (based on the neurocognitive test variables) and Bayesian latent class analysis (LCA) models (without constraints) were used to explore patterns of cognitive performance among community-dwelling older individuals. Gender, age and number of school years were explored as variables. Three cognitive dimensions were identified: general cognition (MMSE), memory (MEM) and executive (EXEC) function. Based on these, three latent classes of cognitive performance profiles (LC1 to LC3) were identified among the older adults. These classes corresponded to stronger to weaker performance patterns (LC1>LC2>LC3) across all dimensions; each latent class denoted the same hierarchy in the proportion of males, age and number of school years. Bayesian LCA provided a powerful tool to explore cognitive typologies among healthy cognitive agers.The study is integrated in the "Maintaining health in old age through homeostasis (SWITCHBOX)" collaborative project funded by the European Commission FP7 initiative (grant HEALTH-F2-2010-259772). NS and JAP are main team members of the European consortium SWITCHBOX (http://www.switchbox-online.eu/). NCS is supported by a SwitchBox post-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels

The utilization of appropriate osteoporosis medications improves following a multifaceted educational intervention: the Canadian quality circle project (CQC)

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is a serious but treatable condition. However, appropriate therapy utilization of the disease remains suboptimal. Thus, the objective of the study was to change physicians' therapy administration behavior in accordance with the Osteoporosis Canada 2002 guidelines.</p> <p>Methods</p> <p>The Project was a two year cohort study that consisted of five Quality Circle (QC) phases that included: 1) Training & Baseline Data Collection, 2) First Educational Intervention & First Follow-Up Data Collection 3) First Strategy Implementation Session, 4) Final Educational Intervention & Final Follow-up Data Collection, and 5) Final Strategy Implementation Session. A total of 340 family physicians formed 34 QCs and participated in the study. Physicians evaluated a total of 8376, 7354 and 3673 randomly selected patient charts at baseline, follow-up #1 and the final follow-up, respectively. Patients were divided into three groups; the high-risk, low-risk, and low-risk without fracture groups. The generalized estimating equations technique was utilized to model the change over time of whether physicians</p> <p>Results</p> <p>The odds of appropriate therapy was 1.29 (95% CI: 1.13, 1.46), and 1.41 (95% CI: 1.20, 1.66) in the high risk group, 1.15 (95% CI: 0.97, 1.36), and 1.16 (95% CI: 0.93, 1.44) in the low risk group, and 1.20 (95% CI: 1.01, 1.43), and 1.23 (95% CI: 0.97, 1.55) in the low risk group without fractures at follow-up #1 and the final follow-up, respectively.</p> <p>Conclusion</p> <p>QCs methodology was successful in increasing physicians' appropriate use of osteoporosis medications in accordance with Osteoporosis Canada guidelines.</p

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group

BACKGROUND: The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women. METHODS: To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m(2). RESULTS: Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m(2), those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 – 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 – 38.4). CONCLUSIONS: These results suggest that differences in body composition may potentially influence kyphosis

Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

<p>Abstract</p> <p>Background</p> <p>Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.</p> <p>Methods</p> <p>Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3).</p> <p>Results</p> <p>The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis.</p> <p>Conclusion</p> <p>Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.</p